NM_002043.5:c.221-271T>C

Variant names:

• chr6-89271993-A-G
• rs282115
• NM_002043.5:c.221-271T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002043.5(GABRR2):​c.221-271T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.954 in 152,330 control chromosomes in the GnomAD database, including 69,436 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.95 (69436 hom., cov: 32)
• Consequence: GABRR2 NM_002043.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.34
• Publications: 5 publications found

Genes affected

GABRR2 (HGNC:4091): (gamma-aminobutyric acid type A receptor subunit rho2) Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA receptors, which are ligand-gated chloride channels. The protein encoded by this gene is a member of the rho subunit family and is a component of the GABA type A receptor complex. This gene exists on chromosome 6q next to the gene encoding the rho 1 subunit of the GABA type A receptor, in a region thought to be associated with susceptibility for psychiatric disorders and epilepsy. Polymorphisms in this gene may also be associated with alcohol dependence, and general cognitive ability. [provided by RefSeq, Apr 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002043.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRR2	NM_002043.5	MANE Select	c.221-271T>C		intron	N/A	NP_002034.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRR2	ENST00000402938.4	TSL:1 MANE Select	c.221-271T>C		intron	N/A	ENSP00000386029.4
	GABRR2	ENST00000602808.1	TSL:3	n.355-271T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.954 AC: 145264 AN: 152212 Hom.: 69377 Cov.: 32

Gnomad AFR AF: 0.984

Gnomad AMI AF: 0.968

Gnomad AMR AF: 0.977

Gnomad ASJ AF: 0.950

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.954

Gnomad FIN AF: 0.947

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.928

Gnomad OTH AF: 0.967

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.954 AC: 145382 AN: 152330 Hom.: 69436 Cov.: 32 AF XY: 0.956 AC XY: 71241 AN XY: 74482

African (AFR) AF: 0.984 AC: 40921 AN: 41566

American (AMR) AF: 0.977 AC: 14963 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.950 AC: 3300 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5188 AN: 5192

South Asian (SAS) AF: 0.953 AC: 4597 AN: 4822

European-Finnish (FIN) AF: 0.947 AC: 10055 AN: 10620

Middle Eastern (MID) AF: 0.990 AC: 291 AN: 294

European-Non Finnish (NFE) AF: 0.928 AC: 63139 AN: 68030

Other (OTH) AF: 0.967 AC: 2047 AN: 2116

Alfa AF: 0.936 Hom.: 39881

Bravo AF: 0.959

Asia WGS AF: 0.986 AC: 3431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.017
DANN	Benign	0.43
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs282115; hg19: chr6-89981712;